A Study of Selinexor in Combination With Standard of Care Therapy for Newly Diagnosed or Recurrent Glioblastoma

Conditions

• Glioblastoma Multiforme

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Selinexor — DRUG
  Dose and Formulation: 20 milligram (mg); Tablet Route of Administration: Oral
• Temozolomide (TMZ) — DRUG
  Dose strength and Formulation: 5, 20, 100, 140, 180, or 250 mg; Capsule Route of Administration: Oral
• Lomustine (CCNU) — DRUG
  Dose and Formulation: 10, 40, or 100 mg; Capsule Route of Administration: Oral
• Standard Fractionated Radiation therapy (RT) — RADIATION
  Radiation Therapy Oncology Group (RTOG) or European Organisation for Research and Treatment of Cancer (EORTC) methodologies of approximately 60 Gy in 30 fractions.
• Bevacizumab — DRUG
  Dose and Formulation: 10 mg/kg; Route of Administration: Intravenous
• TTField — DEVICE
  Dose and Formulation: 200 kHz ≥18h/day; Route of administration: Scalp application of transducer arrays.
• Carmustine — DRUG
  Dose and Formulation: 150 or 200 mg/m\^2; Route of Administration: Intravenous

Study Details

This is a Phase 1/2 study of selinexor in combination with standard of care (SoC) therapy for newly diagnosed glioblastoma (nGBM) or recurrent glioblastoma (rGBM). This study will be conducted in 2 phases: a Phase 1a dose finding study followed by Phase 1b (dose expansion) and a Phase 2 randomized efficacy exploration study and will independently evaluate 3 different combination regimens in 3 treatment arms in patients with nGBM (Arms A and B) or with rGBM (Arm C). * Arm A: evaluating the combination of selinexor with radiation therapy (S-RT) in nGBM participants with uMGMT * Arm B: evaluating the combination of selinexor with radiation therapy and temozolomide (TMZ) (S-TRT) in nGBM participants with methylated-O6-methylguanine-DNA-methyltransferase (mMGMT) * Arm C: evaluating the combination of selinexor with lomustine (or carmustine, if lomustine is not available) (S-L/C) in rGBM participants regardless of MGMT status * Arm D: evaluating the combination of selinexor with bevacizumab in rGBM participants regardless of MGMT status * Arm E: evaluating the combination of selinexor with tumor treating fields (TTField) in rGBM participants regardless of MGMT status

Key Dates

Start date

Jun 8, 2020

Status verified

Nov 2024

Primary completion

Jul 3, 2023

Completion

Jul 3, 2023

Study Design

Enrollment

74 participants (actual)

Allocation

RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

TREATMENT

Arms

• Experimental: Phase 1: Arm A: Selinexor+Radiation Therapy
  Participants with nGBM uMGMT will receive 60 to 80 milligram (mg) of selinexor oral tablet once weekly (QW) across dose level -1, 1, 2, and 3 in combination with 2 Gray (Gy) radiation therapy (RT) daily for 5 days per week in a 42-day cycle during Cycle 1 radiation period followed by 80 mg of selinexor oral tablet on Day 1 and 15 in a 28-day Cycle 2 and subsequently will continue at 80 mg QW until progressive disease (PD) during adjuvant therapy period.
• Active Comparator: Arm A Control: Temozolomide+Radiation Therapy
  Participants with nGBM uMGMT will receive 75 milligram per meter square (mg/m\^2) of temozolomide oral capsule once daily (QD) in combination with 2 Gy RT daily for 5 days per week in a 42-day cycle during Cycle 1 radiation period followed by 150 mg/m\^2 (started from Cycle 3) and increase to 200 mg/m\^2 as tolerated per Investigator's judgment, daily for 5 days in a 28-day cycle during Cycles 4 to 8 cycles during adjuvant therapy period.
• Experimental: Phase 1: Arm B: Selinexor+Temozolomide+Radiation Therapy
  Participants with nGBM mMGMT will receive 40-80 mg of selinexor oral tablet QW across dose level -1, 1, 2, 2a, 2b and 3a and 75 mg/m\^2 of temozolomide oral capsule QD in combination with 2 Gy RT daily for 5 days per week in a 42-day cycle during Cycle 1 radiation period followed by 60 mg (dose level 2a) or 80 mg (dose level 2b and 3a) of selinexor oral tablet on Day 1 and 15 in a 28-day Cycle 2, followed by 150 mg/m\^2 (started from Cycle 3) and increase to 200 mg/m\^2 as tolerated per Investigator's judgment, daily for 5 days in a 28-day cycle during Cycle 4 to 8 during adjuvant therapy period. Participants will continue selinexor weekly per dose level assigned until PD.
• Active Comparator: Arm B Control: Temozolomide+Radiation Therapy
  Participants with nGBM mMGMT will receive 75 mg/m\^2 of temozolomide oral capsule QD in combination with 2 Gy RT daily for 5 days per week in a 42-day cycle during Cycle 1 radiation period followed by 150 mg/m\^2 (started from Cycle 3) and increase to 200 mg/m\^2 as tolerated per Investigator's judgment, daily for 5 days in a 28-day cycle during Cycles 4 to 8 during adjuvant therapy period.
• Experimental: Arm C: Selinexor+Lomustine/Carmustine
  Participants with rGBM uMGMT or mMGMT will receive 40-80 mg of selinexor oral tablet QW across dose level -1, 1, 2, 2a, and 3 and 90-110 mg/m\^2 of lomustine or 150-200 mg/m\^2 of carmustine (substituted if lomustine is not available) capsule on Day 1 of each cycle across dose level -1, 1, 2, 2a, and 3 in a 42-day cycle for all cycles.
• Active Comparator: Arm C Control: Lomustine/Carmustine
  Participants with rGBM uMGMT or mMGMT will receive 110 mg/m\^2 of lomustine or 200 mg/m\^2 of Carmustine (substituted if lomustine is not available) capsule on Day 1 of each cycle in a 42-day cycle for all cycles.
• Experimental: Arm D: Selinexor+Bevacizumab
  Participants with rGBM will receive 60-80 mg of selinexor oral tablet QW across dose level -1, 1 and 10 mg/kg of Bevacizumab intravenous (IV) infusion every 2 weeks (Q2W) in 28-day cycle for all cycles.
• Experimental: Arm E: Selinexor+TTField
  Participants with rGBM will receive 60-80 mg of selinexor oral tablet QW across dose level -1, 1 and will receive scalp application of 200 kilohertz (kHz) of transducer array ≥18 hours/day daily for each cycle in 28 day cycle for all cycles.

Primary Outcome Measure

Phase 1a and 1b: Maximum Tolerated Dose of Selinexor [ Time Frame: At Cycle 1 (up to 42 days) ]

Locations (17)

Find similar trials in Birmingham, AL

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